Tautomerism enol-imine

UV, 1H, and 13C NMR investigations revealed that 5,7,8,9-tetrahydro and 1,2,3,4,5,7,8,9-octahydro tautomeric forms are predominant for 6-ethoxalyl derivatives 23 and 24, while the lower homologs, the pyrrolidino[2,l-Z>]-quinazolin-10-ones, exist in the enol-imine forms [89JCS(P2)1613]. 

C NMR data indicated the presence of a mobile formyl-enamine and enol-imine tautomeric mixture with the predominance of the former at 6-formyl-l,2,3,4,5,7,8,9-octahydro-ll//-pyrido[2,l-b]quinazolin-ll-ones (87JHC1045). 

When dihydro-1,3-benzothiazine 203 was allowed to react with KF in DMF (or NaOMe in MeOH), an open ring tautomeric isomer 204 was formed. When 2-bromoacetophenone 169 (R = H) is present in the reaction medium, a mixture of two diastereoisomers of 206 was obtained (75%) after enolate/imine addition of intermediate 205 with a slight excess of the m-isomer 206a over the trans-isomer 206b (Scheme 35). The same result was obtained by a synthesis from [6+1] fragments, reported in the next section <1995TL753>. 

For several tautomeric systems ketones/enols, imines/enamin and others) a distinct reversal of the stability order is observed when going from the neutral compounds to the radical cations, the first use of which in a new preparative a-Umpolung reaction has been documented for keto/enol systems. The present review provides a critical evaluation of the chemistry of enol radical cations in solution with a special emphasis on the Umpolung reaction and the intermediates thereof. Other enol type of radical cations are discussed with respect to their potential to provide a-carbonyl radical and a-carbonyl cation intermediates. Hence, this article does not constitute a comprehensive summary on all enol type of radical cation reactions. All potentials in this review are referenced versus SCE, unless noted otherwise. Potentials measured against the ferrocene/ferrocenium couple were converted to SCE by adding 0.334 V. 

Thus, it was shown that the tautomerization may be of importance in the thermal dehalogenation of chloroaromatics14. The formation of diarylamines in this reaction can be also explained by the presence of aniline tautomers in the reaction mixtures14. One of the well-known types of aniline tautomerism is the enol-imine-keto-amine equilibrium. In effect, it is a reversible conversion of Schiff bases into enamines that is frequently employed for the synthesis of photochromic compounds, as well as of mesomorphic... 

The equilibrium in the case of Schiff bases prepared from salicylaldehyde and 2-amino-, 2,3-diamino-, 2,6-diamino- and 3-aminomethylpyridine was studied by means of NMR, UV and IR spectroscopy and X-ray crystallography It was shown that the enol-imines were the predominant form in non-polar solvents, whereas in polar solvents a rapid tautomeric interconversion between the enol-imines and the keto-enamines as well as a slow hydrolysis were observed. The tendency to tautomeric interconversion was significant for the 2-(3-pyridylmethyliminomethyl)phenol 45 while in the case of other Schiff bases it was very low. 

This is where we meet the famous double helix immortalised by many books, articles, television programmes and of course films. The DNA double helix is the key element of DNA three dimensional structure. In the 1950s, when James Watson and Francis Crick first proposed the double helix as the key piece of DNA three dimensional structure, they generated enormous scientific and popular excitement, since for the first time the inheritance of genetic information could be understood explicitly in terms of a real chemical structure In order to appreciate this structure, there is a requirement to understand more about the heterocyclic bases (see Section 1.4.1) and their unrivalled capacity for specific hydrogen bonding. All these bases are aromatic but paradoxically prefer keto/amine to enol/imine tautomeric forms... 

Nuclear magnetic resonance studies were also made of Schiff bases obtained from amines and aliphatic /9-diketones. These compounds can exist in any of three tautomeric forms, the keto-imine (10), the keto-enamine (11) and the enol-imine (12) . It was found that in... 

Fig. 15 The IRMPD spectrum (solid black lines) of the Ci anion from AlaPhe compared to the computed IR spectra (blue dotted lines) for putative structures deprotonated at (a) the C-terminal amide, (b) the a-carbon, (c) the N-terminus, and (d) the C-terminal amide with enol-imine tautomerization. Reprinted from Grzetic and Oomens [37], Copyright 2012, with permission from Elsevier...

On the basis of IR and NMR spectral data it was shown that of the three possible tautomeric forms (bis-keto-imine, bis-enol-imine, bis-keto-enamine), quinoxaline 208a adopts the bis-keto-enamine form. Of the six possible tautomeric forms (every two of keto-imine/keto-enamine, hydroxyl-ene-imine/keto-ene-amine, keto-enamine/enol-imine forms) in quinoxaline 210 the hydroxyl-ene-imine/keto-ene-amine form is adopted (Waring et al. 2002). The structures of compounds 208a and 210 were also confirmed by X-ray analysis and deduced from theoretical calculations of the possible limiting stractures (Fig. 2.19) (Waring et al. 2002). 

Ledbette JW (1966) Spectroscopic evidence for enol imine-keto enamine tautomerism of N-(0- and P-hydroxybenzylidene) anils in solution. J Phys Chem 70 2245... 

Compounds show enol imine-enamine tautomerization (Scheme 8). 

Enol imine-enaminone and phenol—quinone tautomerism in (arylazo) naphthols and in analogous Schiff bases were studied by Fabian et al. [92, 93]. In all these molecules there is a favorable N- -H- -O intramolecular hydrogen bond. Depending on the X-H sigma bond (X = N, O), there are two possible tautomers in solution. The solvent effect was calculated on the equilibrium [92], and a combined effect of the solvent and the benzene substituent was studied in [93]. While the FEP/MC simulations provided consistent organic solvent effects in accord with the experimental results [92], the wide spectrum of the solvent-effect calculation methods could predict rather diverse results for several groups of systems in [93]. 

Unlike the products of condensation of 1,2-diaminoethane and 1-amino-2-hydroxyethane with aminobutynones, which exist almost exclusively in the enole form, benzoxazoles 359,361 and benzothiazoles 360,362 are present in the solution as a tautomeric mixture of the ketone (359, 360) and enole (361,362) forms. This seems to be related to weakening of the imine nitrogen basicity due to adjacent oxygen and sulfur atoms. 

Base catalyzed nitrile hydrolysis involves nucleophilic addition of hydroxide ion to the polar C N bond to give an imine anion in a process similar to nucleophilic addition to a polar C=0 bond to give an alkoxide anion. Protonation then gives a hydroxy imine, which tautomerizes (Section 8.4) to an amide in a step similar to the tautomerization of an enol to a ketone. The mechanism is shown in Figure 20.4. 

The first step in either direction consists of addition of NaHS03 to one of the double bonds of the ring, which gives an enol (or enamine) that tautomerizes to the keto (or imine) form. The conversion of 12 to 13 (or vice versa) is an example of 16-12 (or... 

Primary amines add to triple bonds to give enamines that have a hydrogen on the nitrogen and (analogously to enols) tautomerize to the more stable imines ... 

Reactions of Halogenation and Nitrosation Nitrones with protons in the a-alkyl group can occur in tautomeric nitrone-hydroxylamine equilibrium (Scheme 2.117) similar to keto-enol and imine-enamine tautomerisms. 

Fig. 6.25. Simplified mechanism of two degradation reactions between peptides and reducing sugars occurring in solids, a) Maillard reaction between a side-chain amino (or amido) group showing the formation of an imine (Reaction a), followed by tautomerization to an enol (Reaction b) and ultimately to a ketone (Reaction c). Reaction c is known as the Amadori rearrangement (modified from [8]). b) Postulated mechanism of the reaction between a reducing sugar and a C-terminal serine. The postulated nucleophilic addition yields an hemiacetal (Reaction a) and is followed by cyclization (intramolecular condensation Reaction b). Two subsequent hydrolytic steps (Reactions c and d) yield a serine-sugar conjugate and the des-Ser-peptide...

There is a distinct relationship between keto-enol tautomerism and the iminium-enamine interconversion it can be seen from the above scheme that enamines are actually nitrogen analogues of enols. Their chemical properties reflect this relationship. It also leads us to another reason why enamine formation is a property of secondary amines, whereas primary amines give imines with aldehydes and ketones (see Section 7.7.1). Enamines from primary amines would undergo rapid conversion into the more stable imine tautomers (compare enol and keto tautomers) this isomerization cannot occur with enamines from secondary amines, and such enamines are, therefore, stable. 

The optical properties of the 8-o-PhOH-purine adducts have provided insight into their ground-state structures at the nucleoside level. These adducts have the ability to phototautomerize, through an excited-state intramolecular proton transfer (ESIPT) process, to generate the keto form. This tautomerization depends on the presence of a intramolecular hydrogen (H)-bond between the phenolic OH and the imine nitrogen (N-7). Figure 14 shows normalized absorption and emission spectra for 8-o-PhOH-dG and 8-o-PhOH-dA in aqueous buffered water and hexane. In water, 8-o-PhOH-dG shows only enol emission at 395 nm, while 8-o-PhOH-dA shows enol emission at 374 nm and phenolate emission at 447 nm. In hexane, both adducts show keto emission at 475 nm 8-o-PhOH-dA also shows a small amount of enol emission and no phenolate emission. These results show that in water, the intramolecular H-bond... 

The solid-state interaction of enamines (428, 333a) with trans-l,2-diben-zoylethene (87) provides quantitative yields of the pyrrole derivatives 445 or 446 [140]. These remarkable 5-cascades consist of initial vinylogous Michael addition, enol/keto tautomerism, imine/enamine tautomerism, cyclization, and elimination, all within the crystal without melting. A waste-free extraordinary atom economy is achieved that cannot nearly be obtained in solution. The milling times are unusually long here (3 h) but it s certainly worth the effort... 

The first step in either direction consists of addition of NaHSO-, to one of the double bonds of the ring, which gives an enol (or enamine) that tautomerizes to the keto (or imine) form. The conversion of 10 to 11 (or vice versa) is an example of 6-14 (or 6-2). Evidence for this mechanism was the isolation of 10 " and the demonstration that for p-naphthol treated with ammonia and HSOj. the rate of the reaction depends only on the substrate and on HSOi. indicating that ammonia is not involved in the rate-determining step.112 If the starting compound is a (i-naphthol, the intermediate is a 2-keto-4-suIfonic acid compound, so the sulfur of the bisulfite in either case attacks meta to the OH or NH2-m... 

Perhaps the most useful part of the reported synthesis is the facile preparation of (—)-pyrimidoblamic acid (12 Scheme 3). A key to this synthesis is the preparation of the fully substituted pyrimidine 8. This was done by a one-pot inverse electron demand Diels-Alder reaction between the symmetrical triazine 7 and prop-1-ene-1,1-diamine hydrochloride, followed by loss of ammonia, tautomerization, and loss of ethyl cyanoformate through a retro-Diels-Alder reaction. Selective low-temperature reduction of the more electrophilic C2 ester using sodium borohydride afforded 9, the aldehyde derivative of which was condensed with 7V -Boc-protected (3-aminoalaninamide to give the imine 10. Addition of the optically active A-acyloxazolidinone as its stannous Z-enolate provided almost exclusively the desired anti-addition product 11, which was converted into (—)-pyrimidoblamic acid (12). Importantly, this synthesis confirmed Umezawa s assignment of absolute configuration at the benzylic center. 

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